Aerobic glycolysis of bronchial epithelial cells rewires Mycoplasma pneumoniae pneumonia and promotes bacterial elimination.

The immune response to Mycoplasma pneumoniae infection plays a key role in clinical symptoms. Previous investigations focused on the pro-inflammatory effects of leukocytes and the pivotal role of epithelial cell metabolic status in finely modulating the inflammatory response have been neglected. Herein, we examined how glycolysis in airway epithelial cells is affected by M. pneumoniae infection in an in vitro model. Additionally, we investigated the contribution of ATP to pulmonary inflammation. Metabolic analysis revealed a marked metabolic shift in bronchial epithelial cells during M. pneumoniae infection, characterized by increased glucose uptake, enhanced aerobic glycolysis, and augmented ATP synthesis. Notably, these metabolic alterations are orchestrated by adaptor proteins, MyD88 and TRAM. The resulting synthesized ATP is released into the extracellular milieu via vesicular exocytosis and pannexin protein channels, leading to a substantial increase in extracellular ATP levels. The conditioned medium supernatant from M. pneumoniae-infected epithelial cells enhances the secretion of both interleukin (IL)-1ß and IL-18 by peripheral blood mononuclear cells, partially mediated by the P2X7 purine receptor (P2X7R). In vivo experiments confirm that addition of a conditioned medium exacerbates pulmonary inflammation, which can be attenuated by pre-treatment with a P2X7R inhibitor. Collectively, these findings highlight the significance of airway epithelial aerobic glycolysis in enhancing the pulmonary inflammatory response and aiding pathogen clearance.

Metal-Organic Frameworks-Based Frustrated Lewis Pairs for Selective Reduction of Nitroolefins to Nitroalkanes.

Nitroalkanes serve as essential intermediates in the synthesis of pharmaceuticals, agrochemicals, and functional materials. To date, nitroalkanes are mainly prepared from homogeneous catalysts such as noble transition metal catalysts with poor recyclability. Herein, we propose a metal-organic framework-frustrated Lewis pair (MOF-FLP) heterogeneous catalyst for selectively reducing nitroolefins to nitroalkanes under moderate reaction conditions. MOF enrichment effect can significantly improve the catalytic efficiency compared to homogeneous FLP catalysts. Benefiting from the strong interaction between FLP and MOF, the MOF-FLP catalyst exhibits outstanding recyclability. This work not only provides a convenient route for nitroalkane synthesis but also showcases the potential of porous heterogeneous FLP catalysts, offering inspiration for future catalytic design strategies.

Characterization and stress-responsive regulation of CmPHT1 genes involved in phosphate uptake and transport in Melon (Cucumis melo L.).

BACKGROUND: Phosphorus (P) deficiency, a major nutrient stress, greatly hinders plant growth. Phosphate (Pi) uptake in plant roots relies on PHT1 family transporters. However, melon (Cucumis melo L.) lacks comprehensive identification and characterization of PHT1 genes, particularly their response patterns under diverse stresses. RESULTS: This study identified and analyzed seven putative CmPHT1 genes on chromosomes 3, 4, 5, 6, and 7 using the melon genome. Phylogenetic analysis revealed shared motifs, domain compositions, and evolutionary relationships among genes with close histories. Exon number varied from 1 to 3. Collinearity analysis suggested segmental and tandem duplications as the primary mechanisms for CmPHT1 gene family expansion. CmPHT1;4 and CmPHT1;5 emerged as a tandemly duplicated pair. Analysis of cis-elements in CmPHT1 promoters identified 14 functional categories, including putative PHR1-binding sites (P1BS) in CmPHT1;4, CmPHT1;6, and CmPHT1;7. We identified that three WRKY transcription factors regulated CmPHT1;5 expression by binding to its W-box element. Notably, CmPHT1 promoters harbored cis-elements responsive to hormones and abiotic factors. Different stresses regulated CmPHT1 expression differently, suggesting that the adjusted expression patterns might contribute to plant adaptation. CONCLUSIONS: This study unveils the characteristics, evolutionary diversity, and stress responsiveness of CmPHT1 genes in melon. These findings lay the foundation for in-depth investigations into their functional mechanisms in Cucurbitaceae crops.

Additive Strategy Enhancing In Situ Polymerization Uniformity for High-Voltage Sodium Metal Batteries.

In situ polymerization to prepare quasi-solid electrolyte has attracted wide attentions for its advantage in achieving intimate electrode-electrolyte contact and the high process compatibility with current liquid batteries; however, gases can be generated during polymerization process and remained in the final electrolyte, severely impairing the electrolyte uniformity and electrochemical performance. In this work, an in situ polymerized poly(vinylene carbonate)-based quasi-solid electrolyte for high-voltage sodium metal batteries (SMBs) is demonstrated, which contains a novel multifunctional additive N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA). MSTFA as high-efficient plasticizer diminishes residual gases in electrolyte after polymerization; the softer and homogeneous electrolyte enables much faster ionic conduction. The HF/H2 O scavenge effect of MSTFA mitigates the corrosion of free acid to cathode and interfacial passivating layers, enhancing the cycle stability under high voltage. As a result, the 4.4 V Na||Na3 V2 (PO4 )2 F3 cell employing the optimized electrolyte possesses an initial discharge capacity of 112.0 mAh g-1 and a capacity retention of 91.3% after 100 cycles at 0.5C, obviously better than those of its counterparts without MSTFA addition. This work gives a pioneering study on the gas residue phenomenon in in situ polymerized electrolytes, and introduces a novel multifunctional silane additive that effectively enhances electrochemical performance in high-voltage SMBs, showing practical application significance.

Isolation of Polyethylene Glycol with Larger Molecular Weights via Metal-Organic Frameworks.

Polymer products typically present as mixtures with a range of molecular weights, which notably influence the expression of their properties. In this study, a technique is proposed to separate polyethylene glycol (PEG) mixtures of varying molecular weights using metal-organic frameworks (MOFs), thereby narrowing down their molecular weight distribution. Due to the hydrogen bond interactions between PEG and -OH groups in the pores of NU-1000, NU-1000 can selectively adsorb PEG with larger molecular weights from PEG mixture. This separation method consistently yields with narrower molecular weight distribution across multiple cycles. This is the first application of MOFs in regulating the dispersity (Ð) of polymers in solution, providing a novel approach for separating and purifying mixed molecular weight polymers.

Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway.

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.

Phase-Segregated Ductile Eutectogels with Ultrahigh Modulus and Toughness for Antidamaging Fabric Perception.

Ionogels are extremely soft ionic materials that can undergo large deformation while maintaining their structural and functional integrity. Ductile ionogels can absorb energy and resist fracture under external load, making them an ideal candidate for wearable electronics, soft robotics, and protective gear. However, developing high-modulus ionogels with extreme toughness remains challenging. Here, a facile one-step photopolymerization approach to construct an acrylic acid (AA)-2-hydroxyethylacrylate (HEA)-choline chloride (ChCl) eutectogel (AHCE) with ultrahigh modulus and toughness is reported. With rich hydrogen bonding crosslinks and phase segregation, this gel has a 99.1 MPa Young's modulus and a 70.6 MJ m-3 toughness along with 511.4% elongation, which can lift 12 000 times its weight. These features provide extreme damage resistance and electrical healing ability, offering it a protective and strain-sensitive coating to innovate anticutting fabric with motion detection for human healthcare. The work provides an effective strategy to construct robust ionogel materials and smart wearable electronics for intelligent life.

Clinical value of noninvasive lens advanced glycation end product detection in early screening and severity evaluation of patients with diabetic kidney disease.

BACKGROUND: Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease (DKD). This study explored the value of noninvasively measuring lens AGEs to diagnose and evaluate the severity of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM). METHODOLOGY: A total of 134 T2DM patients admitted to the Fifth People's Hospital of Shanghai from March 2020 to May 2021 were selected randomly. Patients were divided into low-, medium-and high-risk groups according to the risk assessment criteria for DKD progression and into DKD and non-DKD (non-DKD) groups according to the Guidelines for the Prevention and Treatment of Diabetic Nephropathy in China. The concentrations of noninvasive AGEs in the lens in all the groups were retrospectively analyzed. RESULTS: The concentration of noninvasive lens AGEs in the high-risk patients, according to the 2012 guidelines of the Global Organization for Improving the Prognosis of Kidney Diseases, was significantly higher than that in the remaining groups. Regression analysis suggested the value of lens AGEs in diagnosing DKD and evaluating DKD severity. Cox regression analysis indicated that the noninvasive lens AGE concentration was positive correlated with the course of disease. CONCLUSION: The receiver operating characteristic (ROC) curve suggested that using noninvasive lens AGE measurements has clinical value in the diagnosis of DKD (area under the curve 62.4%,95% confidence interval (CI) 52.4%-73.9%, p = 0.014) and in assessing the severity of DKD (area under the curve 83.2%, 95% CI 74.1%-92.3%, P < 0.001). Noninvasive lens AGE testing helps screen T2DM patients for DKD and evaluate the severity of DKD.

Ion-Exchange Reaction-Mediated Hierarchical Dual Z-Scheme Heterojunction for Split-Type Photoelectrochemical Immunoassays.

Photoelectrochemical (PEC) immunoassays with ultrasensitive detection abilities are highly desirable for in vitro PEC diagnosis and biological detection. In this paper, dual Z-scheme PEC immunoassays with hierarchical nanostructures (TiO2@NH2-MIL-125@CdS) are synthesized through epitaxial growth of MOF-on-MOF and further in situ derivatization. The dual Z-scheme configuration not only extends the light absorption range but also increases the redox ability due to the interface structure nanoengineering, which synergistically suppresses bulk carrier recombination and promotes the charge transfer efficiency at the electron level. Furthermore, a smart MOF-derived labeling probe (CuO@ZnO nanocube) is designed to develop a split-type PEC biosensor by using prostate-specific antigen (PSA) as a target biomarker. In the presence of PSA, the Ab2-labeled CuO@ZnO would specifically bond to the dual Z-scheme electrode. Then, the MOF-derived CuO@ZnO is dissolved by hydrochloric acid to release Cu2+, which could replace Cd2+ via an ion-exchange reaction, thus leading to the decrease of the photocurrent due to the destruction of the dual Z-scheme configuration. In typical applications, the split-type PEC immunoassay exhibits an excellent detection performance for PSA with a LOD as low as 0.025 pg·mL-1.

Alteration of the Intestinal Microbial Flora and the Serum IL-17 Level in Patients with Graves' Disease Complicated with Vitamin D Deficiency.

BACKGROUND: Intestinal flora is associated with Graves' disease (GD). This study explored the association of serum 25(OH)D with the diversity of the intestinal flora and serum IL-17 in GD patients. METHODS: Patients newly diagnosed with GD at 2 centers between 2018 and 2021 were consecutively included. According to their 25(OH)D levels, they were divided into the deficiency group, the insufficiency group, and the sufficiency group. Some patients with vitamin D deficiency or insufficiency were randomly selected and were matched with healthy volunteers (normal control [NC]) in terms of sex, age, and case number. The diversity and differential species of the intestinal flora and serum IL-17 levels were compared. RESULTS: Serum 25(OH)D negatively correlated with serum IL-17, the platelet/lymphocyte ratio, and TSH receptor antibody. The diversity of the intestinal flora decreased in the GD group, with noticeable differences in the composition of the intestinal flora when compared with the NC group. At the phylum level, the GD group exhibited a significantly lower abundance of Firmicutes but a higher abundance of Actinobacteria. At the genus level, the GD group exhibited higher relative abundances of Bifidobacterium, Collinsella, and Pediococcus but lower abundances of Roseburia and Dialister. CONCLUSIONS: The changes in the vitamin D level and the composition of the intestinal flora may partially contribute to the development of GD.

Serum Trimethylamine N-oxide and the Diversity of the Intestinal Microbial Flora in Type 2 Diabetes Complicated by Diabetic Kidney Disease.

BACKGROUND: Trimethylamine N-oxide (TMAO) serves as a metabolite of intestinal bacteria as well as a urotoxin influencing the prognosis of chronic kidney disease (CKD), which has become a research hotspot in the field of kidney disease. This study preliminarily explored the alternations of the microbial flora and serum TMAO in patients with type 2 diabetes mellitus (T2DM) complicated with diabetic kidney disease (DKD). METHODS: Seventeen T2DM patients at the Affiliated Hospital of Zunyi Medical University between September 2018 and February 2019 were included. Among these patients, 8 patients had T2DM complicated with DKD. Eight healthy volunteers constituted the control group. Fresh stool was collected for Illumina sequencing. Based on the sequencing outcomes, the flora diversity and species differences were analyzed. Serum TMAO, cystatin C, urinary albumin/urine creatinine ratios (ACRs), and routine biochemical outcomes were also compared. RESULTS: The DKD group exhibited a significantly higher TMAO level than the remaining groups. The high-TMAO group had a significantly increased ACR level compared with the low-TMAO group. TMAO positively correlated with the ACR. Compared with the control group, the DKD group exhibited a decreased flora diversity. At the genus level, both the T2DM group and the DKD group showed decreased numbers of Alloprevotella and Megasphaera compared with the control group. The difference in Megasphaera between the DKD group and the control group was significant. CONCLUSIONS: The alternation of the intestinal microbial flora may participate in the development of DKD, and TMAO and chronic inflammation might be important factors for DKD development.

GESTATIONAL WEIGHT GAIN AS AN INDEPENDENT RISK FACTOR FOR MACROSOMIA IN WOMEN WITH INTERMEDIATE STATE GESTATIONAL BLOOD GLUCOSE.

Objective: Macrosomia is closely associated with gestational diabetes mellitus (GDM) but its relationship with maternal intermediate state gestational blood glucose (ISGBG; normal fasting blood glucose and 7.8 mmol/L <1 hour blood glucose [BG] <10 mmol/L or 6.7 mmol/L <2 hour BG <8.5 mmol/L) is unclear. Here, we analyzed the clinical characteristics and pregnancy outcomes and explored risk factors for macrosomia in women with ISGBG. Methods: A total of 847 women with normal glucose tolerance gestation, 330 with ISGBG, and 99 with GDM were included. Maternal and fetal clinical data were collected and 3-point BG following oral glucose tolerance test, fasting insulin, glycated hemoglobin, and blood lipids profile were measured. Results: The incidence rate of macrosomia among the neonates of women with ISGBG was as high as 10.9%. In the ISGBG group, prepregnancy body mass index (BMI), gestational weight gain (GWG) and the proportion of women with excessive GWG (eGWG) were significantly higher in women with macrosomia compared with those who delivered a normal weight neonate. In women with ISGBG, neonate weight was positively correlated with maternal prepregnancy weight (r = 0.183, P<.01), prepregnancy BMI (r = 0.135, P<.01), and GWG (r = 0.255, P<.01), and negatively correlated with high-density lipoprotein cholesterol (r = -0.172, P<.01). Nonetheless, only eGWG was an independent risk factor (odds ratio = 3.18, 95% confidence interval = 1.26 to 7.88, P<.05) for macrosomia. The risk of macrosomia in pregnant women with prepregnancy BMI <25 kg/m2 or BMI ≥25 kg/m2 and eGWG was 3.39 and 3.27 times, respectively. Conclusion: The incidence rate of macrosomia is increased in women with ISGBG and eGWG is the strongest independent risk factor. In order to reduce the risk for macrosomia, timely lifestyle intervention to promote appropriate weight gain during pregnancy deserves evaluation. Abbreviations: AUC = area under the curve; BG = blood glucose; 1 hour BG = 1 hour blood glucose after OGTT; 2 hour BG = 2 hour blood glucose after OGTT; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; FBG = fasting blood glucose; FINS = fasting insulin; GDM = gestational diabetes mellitus; HbA1c = glycated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance index; ISGBG = intermediate state gestation blood glucose; LDL-C = low-density lipoprotein cholesterol; Ln = natural logarithm; MLBW = mature low birth weight; NGTG = normal glucose tolerance gestation; OGTT = oral glucose tolerance test; OR = odds ratio; SD = standard deviation.

Berberine (BBR) Attenuated Palmitic Acid (PA)-Induced Lipotoxicity in Human HK-2 Cells by Promoting Peroxisome Proliferator-Activated Receptor α (PPAR-α).

BACKGROUND Berberine (BBR), a natural alkaloid isolated from Coptis chinensis, has frequently been reported as an antidiabetic reagent, partly due to its lipid-lowering activity. Evidence suggests that BBR ameliorates palmitate-induced lipid deposition and apoptosis in renal tubular epithelial cells (TECs), which tracks in tandem with the enhancement of peroxisome proliferator-activated receptor alpha (PPAR-alpha). The study aim was to investigate the roles of BBR in renal lipotoxicity in vitro, and investigate whether PPAR-alpha was the underlying mechanism. MATERIAL AND METHODS Human TECs (HK-2 cells) were injured with palmitic acid (PA), and then treated with BBR, BBR+PPAR-alpha inhibitor (GW6471), and PA+PPAR-alpha agonist (fenofibrate). Endoplasmic reticulum (ER) stress was assessed by measuring the expression of prospective evaluation of radial keratotomy (PERK), C/EBP-homologous protein (CHOP), and 78 kDa glucose-regulated protein (GRP78). Lipid metabolism was assessed by determining lipid anabolism-associated genes, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL), as well as lipid catabolism-associated gene, including carnitine palmitoyl transferase 1 (CPT1). Inflammatory response of HK-2 cells was evaluated by measuring interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Cell apoptosis and protein levels of cleaved-caspase-3 were evaluated. RESULTS PA downregulated PPAR-alpha and induced server lipotoxicity in HK-2 cells by ER stress, increasing lipid deposition, and elevating inflammatory response of HK-2 cells accompanied with inducting cell apoptosis and cleaved-caspase-3, which were obviously reversed by additional treatment of BBR or PPAR-alpha agonist. However, the protective effect of BBR in PA-induced lipotoxicity in HK-2 cells was significantly ameliorated by PPAR-alpha inhibitor. CONCLUSIONS BBR attenuated PA-induced lipotoxicity via the PPAR-alpha pathway.

Association of High Prolactin Level on Postoperative Day 1 and Tumor Invasion with Female Gonadal Dysfunction After Trans-Sphenoidal Surgery of Pituitary Adenomas.

BACKGROUND The aim of this study was to evaluate the risk factors of gonadal dysfunction among Chinese women of reproductive age with pituitary adenomas (PAs) after trans-sphenoidal surgery. MATERIAL AND METHODS We retrospectively evaluated 317 women (16-44 years old) who underwent gonadal function and hormone testing before and after trans-sphenoidal surgery for PAs during 2003-2012. Gonadal function was assessed on the basis of menstrual status. RESULTS Three women were excluded because of pre-existing gynecological diseases. Before trans-sphenoidal surgery, 34 (10.7%) women were eugonadal and 283 (89.3%) women had gonadal dysfunction. After trans-sphenoidal surgery, 130/189 (68.7%) women with follow-up menstruation data were eugonadal, and 59/189 (31.2%) women exhibited gonadal dysfunction. In addition, 67.4% women of reproductive age with PAs and gonadal dysfunction were restored by trans-sphenoidal surgery (P<0.01). Postoperative gonadal dysfunction was independently associated with high prolactin level at day 1 after trans-sphenoidal surgery (odds ratio (OR)=1.024; 95% confidence interval (CI)=1.005-1.043; P=0.012) and tumor invasion (OR=5.752; 95%CI=1.618-20.447; P<0.01). Based on the receiver operating characteristic (ROC) curve, prediction of gonadal dysfunction in women of reproductive age after trans-sphenoidal surgery for PAs using prolactin >46.82 µg/L on postoperative day 1 had sensitivity of 88%, specificity of 95%, positive predictive value of 98%, and negative predictive value of 76%, and an area under the ROC curve of 0.701. CONCLUSIONS Gonadal dysfunction is very common in Chinese women of reproductive age with PAs and can be effectively restored by trans-sphenoidal surgery. Prolactin >46.82 µg/L at 1 day after trans-sphenoidal surgery and tumor invasion can predict postoperative gonadal dysfunction in these patients.

Development of a facile and sensitive HPLC-FLD method via fluorescence labeling for triterpenic acid bioavailability investigation.

Triterpenic acids are widely distributed in many fruits and are known for their medicinal benefits. The study of bioavailability has been an important task for a better understanding of the triterpenic acids. Although many methods based on fluorescence labeling for triterpenic acid determination have been established, these reported methods needed anhydrous conditions, which are not suitable for the convenient study of triterpenic acid bioavailability. Inspired by that, a versatile method, which overcomes the difficulty of the reported methods, has been first developed in this study. The novel method using 2-[12-benzo[b]acridin-5- (12H)-yl]-acetohydrazide (BAAH) as the fluorescence labeling reagent coupled with high-performance liquid chromatography with fluorescence detection was first developed for the study of triterpenic acid bioavailability. Furthermore, the labeling conditions have been optimized in order to achieve the best fluorescence labeling yield. Under the optimal conditions, the quantitative linear range of analytes was 2-1000 ng mL-1 , and the correlation coefficients were >0.9998. The detection limits for all triterpenic acid derivatives were achieved within the range of 0.28-0.29 ng mL-1 . The proposed method was successfully applied to the study of triterpenic acid bioavailability with excellent applicability and good reproducibility.

A memristive-photoconductive transduction methodology for accurately nondestructive memory readout.

Crossbar resistive memory architectures enable high-capacity storage and neuromorphic computing, accurate retrieval of the stored information is a prerequisite during read operation. However, conventional electrical readout normally suffer from complicated process, inaccurate and destructive reading due to crosstalk effect from sneak path current. Here we report a memristive-photoconductive transduction (MPT) methodology for precise and nondestructive readout in a memristive crossbar array. The individual devices present dynamic filament form/fuse for resistance modulation under electric stimulation, which leads to photogenerated carrier transport for tunable photoconductive response under subsequently light pulse stimuli. This coherent signal transduction can be used to directly detect the memorized on/off states stored in each cell, and a prototype 4 * 4 crossbar memories has been constructed and validated for the fidelity of crosstalk-free readout in recall process.

Vitamin D is involved in the effects of the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys in mice with DKD.

BACKGROUND: Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. METHODS: DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. RESULTS: 1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. CONCLUSIONS: The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.

Increased Circulating IL-32 Is Associated With Placenta Macrophage-derived IL-32 and Gestational Diabetes Mellitus.

OBJECTIVE: Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM. MATERIALS AND METHODS: First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence. RESULTS: First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index. CONCLUSION: Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.

A bionic self-driven retinomorphic eye with ionogel photosynaptic retina.

Bioinspired bionic eyes should be self-driving, repairable and conformal to arbitrary geometries. Such eye would enable wide-field detection and efficient visual signal processing without requiring external energy, along with retinal transplantation by replacing dysfunctional photoreceptors with healthy ones for vision restoration. A variety of artificial eyes have been constructed with hemispherical silicon, perovskite and heterostructure photoreceptors, but creating zero-powered retinomorphic system with transplantable conformal features remains elusive. By combining neuromorphic principle with retinal and ionoelastomer engineering, we demonstrate a self-driven hemispherical retinomorphic eye with elastomeric retina made of ionogel heterojunction as photoreceptors. The receptor driven by photothermoelectric effect shows photoperception with broadband light detection (365 to 970 nm), wide field-of-view (180°) and photosynaptic (paired-pulse facilitation index, 153%) behaviors for biosimilar visual learning. The retinal photoreceptors are transplantable and conformal to any complex surface, enabling visual restoration for dynamic optical imaging and motion tracking.

Meta-analysis of the effect of KCNQ1 gene polymorphism on the risk of type 2 diabetes.

The potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) is a member of 11 mammalian Kv channel families that plays a key role for the repolarization of the cardiac action potential as well as water and salt transport. Genome-wide association studies have identified KCNQ1 as a type 2 diabetes (T2D) susceptibility gene in populations of Asian descent. After that, a number of studies reported that the rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 polymorphism in KCNQ1 has been implicated in T2D risk. However, studies on the association between these polymorphism and T2D remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 114,140 patients and 167,322 controls from 30 published case-control studies was performed. Overall, significantly elevated T2D risk was associated with rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 risk allele when all studies were pooled into the meta-analysis. In the subgroup analysis by ethnicity, sample size, and Hardy-Weinberg equilibrium status of controls, significantly increased risks were found for these polymorphisms. In conclusion, this meta-analysis suggests that rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 polymorphisms in KCNQ1 are associated with elevated T2D risk.